Genetic and immune factors underlying the efficacy of cetuximab and panitumumab in the treatment of patients with metastatic colorectal cancer

Efficacy of monoclonal anti-EGFR antibody (cetuximab, panitumumab) in combination with chemotherapy and alone has been demonstrated in clinical trials in patients withmCRC. Both drugs block signaling EGFR pathway in malignant cells (blocking ligand binding and EGFR dimerization). Receive treatment responses with anti-EGFR agents is possible only in a selected group of patients with mCRC. Successful treatment with cetuximab and panitumabem is possible almost exclusively in patients without RAS mutations. Research of predictive value of EGFR gene copy number, PI3KCA gene mutations, P53 and PTEN and EGFR their ligands concentrations is ongoing. Due to the different molecular structure (IgG1 chimericmonoclonal antibody) and panitumumab (IgG2 humanized antibody) it is possible an additional characteristic of the mechanism of action of cetuximab (antibody dependent cellular cytotoxicity). Therefore predictor cetuximab therapymay be the presence of different polymorphic forms of the genes for receptor immunoglobulin Fc fragments: Fc gamma RIIa and Fc gamma RIII subclasses.